Updated EXPLORER Data Released for Progress of Avapritinib in Patients with Systemic Mastocytosis

Jun 17, 2019 | Rare Diseases, Systemic Mastocytosis


Blueprint Medicines (BPMC) recently released updated data from its ongoing, registration-enabling EXPLORER trial of avapritinib in patients with systemic mastocytosis (SM).  The updated data reveals a confirmed overall response rate (ORR) of 77% in advanced SM patients, as assessed by a central review committee of SM clinical experts.

Systemic Mastocytosis (SM)

This disease is a form of mastocytosis in which mast cells accumulate in internal tissues and organs such as the liver, spleen, bone marrow, and small intestines.  It is typically diagnosed in adults. Signs and symptoms vary based on which parts of the body are affected.  The disorder is usually caused by somatic changes (mutations) in the KIT gene. Most cases are sporadic and not inherited, but familial cases rarely have been reported.

The Study 

This is a Phase 1, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (also known as BLU-285), administered orally (PO), in adult patients with advanced systemic mastocytosis and other relapsed or refractory myeloid malignancies. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).

The protocol called for 80 participants and the participating sites include several prominent academic research centers.

Results Thus Far

The updated data showed a confirmed overall response rate (ORR) of 77 percent in advanced SM patients, as assessed by a central review committee of SM clinical experts. In addition, the data showed durable clinical activity across advanced, smoldering and indolent forms of SM, with patients on therapy up to 34 months and responses continuing to deepen over time. Avapritinib was generally well-tolerated, with most adverse events (AEs) reported by investigators as Grade 1 or 2. The results are being presented today in an oral presentation at the 24th Congress of the European Hematology Association (EHA) in Amsterdam, The Netherlands.

Dr. Deepti Radia is a hematologist and an investigator on the Explorer Trial. She first noted, “I believe that potentially targeting KIT D816V, the disease driver is nearly all systemic mastocytosis patients, represents a promising therapeutic approach.” Moreover, she reports that “These new data show avapritinib led to profound reductions of objective mast cell burden and durable clinical responses across a broad patient population. In advanced systemic mastocytosis, I am particularly encouraged by the strong activity shown in patients with especially poor survival rates, such as those with mast cell leukemia or high-risk genotypes. These data further reinforce the broad potential of avapritinib to address important medical records across the spectrum of the disease.”

About Avapritinib

Avapritinib is an investigational, oral precision therapy that selectively and potently inhibits KIT and PDGFRA mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with GIST, including potent activity against activation loop mutations that are associated with resistance to currently approved therapies.

About Blueprint Medicines (BPMC)

They are a precision medicine company focused on gnomically defined cancers, rare diseases and cancer immunotherapies.   Founded in 2011 by a proven team of scientists and entrepreneurs with world-renowned expertise in the development of targeted cancer therapies, cancer genomics and rational drug development, Blueprint Medicines is poised to realize the promise of the cancer data–truly personalized therapies that improve outcomes and shift cancer to a manageable condition.  They floated their stock in an IPO in 2015.

Lead Research/Investigator

Dr. Deepti Radia  is a hematologist


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